Staphylococcus infections pose a serious health threat to humans, companion animals and livestock. Staphylococcus aureus is a Gram-positive bacterium that can asymptomatically colonize human skin and the anterior nares, but it is also responsible for mild to severe skin and soft tissue infections and life-threatening endocarditis, pneumonia, and sepsis. In 2011, there were approximately 80,000 invasive methicillin-resistant S. aureus (MRSA) infections in the United States that resulted in 11,000 deaths. Although the prevalence of MRSA carriage in companion animals is low (approximately 0-4%) and infections are rare, other Staphylococcus species are common commensals and pathogens in veterinary medicine. S. schleiferi and S. pseudintermedius are the leading causes of skin and ear infections in dogs; S. hyicus causes high-morbidity skin infections in pigs and osteomyelitis in birds, while S. agnetis and S. chromogenes cause mastitis in cattle and are associated with reduced milk quality.
The emergence of drug-resistant Staphylococcus is a global problem. Drugs such as erythromycin and cephalexin are commonly used to treat infections in both humans and animals, leading to concern that as resistance to shared antibiotics becomes more widespread, zoonotic transmission of either drug-resistant Staphylococcus, or horizontal transfer of resistance genes may render these treatments ineffective for both humans and animals. Despite this concern, there is a dearth of knowledge about how Staphylococcus species in veterinary medicine differ from those commonly seen in human medicine.
There is a need in the art to identify novel compounds useful in the treatment of bacterial infections, especially drug-resistant Staphylococcus infections. The present invention addresses this need.